Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms by which administration of the H+,K(+)-ATPase inhibitor B 831-78 or intragastric perfusion with NaHCO3 induces plasma gastrin release were studied in the rat. Experiments were performed after a washout of residual intragastric contents in fasted animals provided with chronic gastric fistulae. Acute and chronic administration of B 831-78 elevated plasma gastrin dose-dependently up to 5-6 times above control levels, while the increase was only twofold with intragastric NaHCO3 infusion despite similar neutralization of gastric acidity. The profound hypergastrinaemia induced by the H+,K(+)-ATPase inhibitor, after both acute and chronic treatment, was completely prevented or reversed by intragastric perfusion with physiological amounts of acid (0.15 N HCl, 2.5 ml/h). The hypergastrinaemia was, however, largely resistant to high doses of atropine (4.3 mumol/kg) and of the M1 selective muscarinic antagonist telenzepine (10 mumol/kg). In contrast, the modest increase in plasma gastrin induced by gastric perfusion with NaHCO3 was completely suppressed by the high atropine dose and was attenuated by small doses of atropine or telenzepine (0.01 mumol/kg and 1 mumol/kg). These results demonstrate that, in the rat, blockade of the H+,K(+)-ATPase can potently induce gastrin release in the absence of a meal. Moreover, they suggest that interruption of the negative feedback between acid and gastrin release is the main mechanism through which this class of drugs releases gastrin in the rat. Since a similar degree of gastrin release cannot be achieved by alkalinization of gastric contents, additional hormonal or neural regulatory factors may contribute to the drug-induced hypergastrinaemia.
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PMID:Effect of acute and chronic acid suppression on plasma gastrin release in the rat. 131 89

Cysteamine, a potent duodenal ulcerogen, stimulates gastric acid and gastrin secretion and decreases immunoreactive somatostatin (IRS) from the gut and hypothalamus of the rat. To elucidate the structural requirements for this effect, we tested a series of cysteamine analogs for their IRS decreasing activity in comparison with their nucleophilic and reducing potencies. Adult female rats were sacrificed 4 hr after p.o. administration of the test chemicals given in molar equivalents to 30 mg/100 g of cysteamine-HCl. IRS decreasing activity in gastric mucosa, expressed as percentage of controls is listed in descending order: cystamine (55%), cysteamine (59%), 2-dimethylaminethanethiol (59%), ethylamine (66%), 1,3-propanedithiol (70%), propylamine (75%) and 3-aminothiophenol (79%). The following thiols and amines had no IRS decreasing effect (80% of controls): L-cysteine, ethanethiol, 1-propanethiol, penicillamine, dimercaprol, 1-4-dithiothreitol, ethanolamine, propionitrile, n-butyronitrile, o-, m- or p-aminophenol. The aryl 2-, 3- or 4-aminothiophenols, unlike most of their aminophenol analogs also decreased immunoreactive prolactin in the pituitary by 38 to 78%. IRS decreasing activity was independent of the reducing potency of cysteamine derivatives but was correlated significantly (r = 0.793, P < .01) with electron affinity of -SH, -NH2, -OH and -CN radicals in terminal alkyl chemicals. The structural requirement for decreasing activity is the presence of either -SH and -NH2 on a 2 to 3 carbon alkyl or aryl molecule. Both radicals when present together increase potency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Somatostatin depleting potency of cysteamine-related thiols and amines in the rat: structure-activity relation. 135 14

On the basis of the existing experimental and clinical studies about the factors affecting the appearance of hypergastrinemia in renal failure, it can be concluded that the kidney plays an important, but not the only, role in the degradation of endogenous gastrin in humans. In this process the key role is played by the blood flow through the kidney, the preservation of the peritubular capillary system, and the functional kidney mass. Glomerular filtration has no particular importance in the extraction of gastrin from the circulation, while through the urine only a small amount of gastrin is excreted. In the decomposition of a part or at least some molecular gastrin forms, an important role is played by the capillary systems of extra-renal tissue. One further conclusion is that hypergastrinemia in patients with renal failure is the result of the combined effects of the reduced catabolism of gastrin in the kidney and its increased synthesis which is for the most part connected with hypochlohydria and secondary hyperparathyroidism. In patients with renal failure there exists the inhibition of the gastrin acid secretion which is the cause of the weakening of the mechanism of the feedback connection between HCl and gastrin, while because of a permanent stimulation of G-cells, the hyperplasia of these cells develops, as well as the increased secretory activity, and hypergastrinemia. Parietal cells become less sensitive to a permanently increased serum gastrin concentration but still capable of reacting to the maximal stimulus. In patients with renal failure, especially those with extreme hypergastrinemia, there develops the increased concentration of large, mainly biologically inactive (big big gastrin, component I) molecular forms of gastrin.
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PMID:Serum gastrin concentration in chronic renal failure. 138 Mar 59

The release of secretin into plasma by intraduodenal (id) infusion of HCl or iso-osmotic (290 mosm l-1) NaCl, and the associated changes of moderately stimulated gastric acid, serum gastrin, two calciotropic hormones, total and 45calcium (Ca), were examined in the rat. The possible role of endogenous secretin as an enterogastrone and as a mediator of the hypothesized endocrine gut-thyroid-parathyroid axis was further characterized with the aid of secretin immunoneutralization and exogenous secretion. The id-HCl-stimulated secretin, measured by a sensitive radioimmunoassay, was accompanied by a decrease in gastric acid secretion, whereas secretin blockage by anti-secretin immune serum resulted in a significant increase in acid secretion. The correlation between plasma secretin and acid output was only slight. Gastrin and Ca metabolism remained unchanged during secretin stimulation. Intravenous synthetic porcine secretin at a dose reported to be effective in other target preparations (2 CU (0.58 microgram) kg-1 h-1) had no effect on gastric acid secretion and Ca metabolism. In contrast, a pharmacological dose, 32 CU (9.3 micrograms) kg-1 h-1, inhibited acid secretion, decreased serum Ca and total protein, and increased serum parathyroid hormone, but left calcitonin and gastrin unchanged. Endogenous secretin appeared to act as an enterogastrone, but whether it was the only one is unclear. No role was detected for secretin in the gut-thyroid-parathyroid axis, since the Ca changes observed may have been unspecifically mediated.
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PMID:Endogenous secretin in the rat--evidence for a role as an enterogastrone but failure to influence serum calcium homeostasis. 138 22

1. This study was designed to determine the involvement of cholecystokinin (CCK) in the gastric secretory responses to exogenous and endogenous secretagogues in conscious dogs with chronic gastric fistulae (GF), pancreatic fistulae (PF) and Heidenhain pouches (HP). 2. A meal of meat or intragastric application of peptone (300 mosM) increased secretion of HCl from the HP and pancreatic secretion of protein and plasma levels of gastrin, CCK and somatostatin. 3. The CCK receptor antagonist L-364,718 caused a further increase in the postprandial HCl secretion from the HP and in the plasma levels of gastrin and CCK but pancreatic output of protein and plasma concentration of somatostatin were significantly reduced. 4. Addition to intragastric peptone of 10% oleate or its acidification to pH 3.0 profoundly inhibited the HP secretion and gastrin release but significantly increased pancreatic secretion of protein and plasma levels of CCK and somatostatin. Administration of L-364,718 reversed the fall in the HP secretion and plasma gastrin while significantly attenuating pancreatic protein secretion and plasma somatostatin levels. 5. Intragastric administration of hyperosmolar (1200 mosM) peptone also inhibited HCl secretion from the HP but this was not affected by L-364,718. 6. Exogenous CCK and bombesin (but not gastrin) caused a small increase in HCl secretion from the HP and marked stimulation of pancreatic protein secretion accompanied by a significant rise in plasma levels of gastrin, CCK and somatostatin. Administration of L-364,718 resulted in a further increase in the HCl response of HP to bombesin and in plasma levels of gastrin and CCK but caused a reduction in plasma levels of somatostatin. 7. We conclude that CCK released by a meal of meat, intragastric peptone, oleate or acidified peptone and intravenous bombesin exerts tonic inhibitory influences on gastric acid secretion and that this effect is mediated, at least in part, by somatostatin.
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PMID:Role of cholecystokinin in the inhibition of gastric acid secretion in dogs. 140 19

This study was designed to determine the role of cholecystokinin (CCK) in the inhibition of gastric HCl secretion by duodenal peptone, fat and acid in dogs with chronic gastric and pancreatic fistulas. Intraduodenal instillation of 5% peptone stimulated both gastric HCl secretion and pancreatic protein secretion and caused significant increments in plasma gastrin and CCK levels. L-364,718, a selective antagonist of CCK-A receptors, caused further increase in gastric HCl and plasma gastrin responses to duodenal peptone but reduced the pancreatic protein outputs in these tests by about 75%. L-365,260, an antagonist of type B receptors, reduced gastric acid by about 25% but failed to influence pancreatic response to duodenal peptone. Addition of 10% oleate or acidification of peptone to pH 3.0 profoundly inhibited acid secretion while significantly increasing the pancreatic protein secretion and plasma CCK levels. Administration of L-364,718 reversed the fall in gastric HCl secretion and significantly attenuated pancreatic protein secretion in tests with both peptone plus oleate and peptone plus acid. Exogenous CCK infused i.v. in a dose (25 pmol/kg per h) that raised plasma CCK to the level similar to that achieved by peptone meal plus fat resulted in similar inhibition of gastric acid response to that attained with fat and this effect was completely abolished by the pretreatment with L-364,718. We conclude that CCK released by intestinal peptone meal, containing fat or acid, exerts a tonic inhibitory influence on gastric acid secretion and gastrin release through the CCK-A receptors.
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PMID:Role of cholecystokinin in the intestinal fat- and acid-induced inhibition of gastric secretion. 147 10

Secretin in known to inhibit gastric acid secretion. Exogenous secretin has also been shown to have a biphasic effect on acid secretion, being stimulatory then inhibitory. To explain this effect, we studied the timing of gastrin, somatostatin, and HCl releases in the gastric lumen in response to an i.v. bolus of secretin (360 pmol) or saline in conscious rats provided with a chronic double gastric fistula and having had or not antrectomy. After secretin but not saline, an immediate and transient increase in acid and gastrin secretions was first observed. After a 4 min lag, a dramatic increase in somatostatin secretion was then observed, together with a 90 percent inhibition of acid secretion and a return of gastrin release to basal level. Twenty min after secretin administration, a rebound increase in acid and gastrin outputs occurred, whereas somatostatin output returned to basal level. The secretin-induced somatostatin release was higher in rats with antrectomy than in those without antrectomy suggesting that the observed somatostatin output mostly originated from the fundus. This present study suggests that a bolus of secretin induced a gastrin release and thus could stimulate acid secretion. These pharmacological findings could provide an explanation for the so-called paradoxical secretin-induced stimulation of gastrin secretion in particular conditions.
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PMID:Sequential somatostatin and gastrin releases in response to secretin in rat in vivo. 168 37

The influence of intragastric pH on the basal release of somatostatin has been studied in healthy controls and in duodenal ulcer patients. In addition the somatostatin response to gastrin-releasing peptide infusion has been evaluated both regarding the effect of intragastric pH and the influence of vagal innervation and muscarinic blockade. No difference was found in basal blood levels, when changing the intraluminal pH, although a slightly higher basal somatostatin concentration was noticed in patients with duodenal ulcer disease. Neither proximal gastric vagotomy nor cholinergic blockade had any effect on basal somatostatin concentrations. GRP infused in stepwise increasing doses from 20 pmol/kg/h to 400 pmol/kg/h induced a small but significant response. This effect of GRP was most evident, when the stomach was perfused with 0.1 M HCl. The small, somatostatin response to GRP infusion was not influenced by vagal denervation of the parietal cell area, neither by cholinergic blockade. Despite the previously observed effects of vagotomy and cholinergic blockade on gastrin release induced by GRP, a corresponding inverse effect on somatostatin is not apparent.
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PMID:Somatostatin release induced by gastrin-releasing peptide in man. Effect of proximal gastric vagotomy and cholinergic blockade. 197 87

Hydrochloric acid is involved in the causation of peptic ulcer, but the exact role has not been defined. Suppression of acid secretion is associated with ulcer healing. The acid secreting cell is the parietal cell, which possesses a proton pump in the secretory membrane; morphologic changes accompany and facilitate the active secretion of hydrochloric acid. Stimulation of acid secretion occurs by three major pathways, which utilize acetylcholine, histamine, and gastrin. The predominant effects of histamine are mediated by adenylate cyclase, whereas those of gastrin and acetylcholine involve cytosolic calcium. There is a complicated arrangement of receptors and pathways that culminate in the activation of the proton pump. The parietal cell is influenced by neurocrine, hormonal, and paracrine mechanisms. Peptides join the more familiar neurotransmitters in affecting the parietal cell. Somatostatin is present in the gut and acts to decrease acid secretion. The hormone gastrin is released, in a feedback fashion, when the antrum is alkalinized. Most stimuli of acid secretion are blocked by H2-antagonists. Inhibitory hormones are released when acid arrives in the intestine. Inhibition of acid secretion can be achieved by influencing the parietal cell at the level of histamine, gastrin, and muscarinic receptors. The proton pump itself can be blocked by drugs that inhibit the final phase of acid secretion.
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PMID:Acid secretion and suppression. 207 93

Peptic ulcer pathophysiology has advanced in several ways during the last years; the following facts has been put forward: a) There has been recognized specific receptors controlling oxyntic cell secretion for histamine, acetylcholine, gastrin and prostaglandins. Agonists and antagonists for the above mentioned receptors has been synthesized. The physiology of the proton-pump located at the luminal side of the mucous membrane has been clarified. This pump is responsible for HCl secretion and can be blocked with omeprazole and trimeprazole. b) There is a comprehensive view of the gastric mucosal barrier, which is important for gastric self-protection, against inner or outer noxious stimuli. The mucosal barrier rupture can be the initial step of some gastroduodenal diseases, so the understanding of its functioning is very important to explain the pathophysiology of peptic ulcer. Finally, some etiopathogenic factors has been proved in the development of peptic ulcer, as Helicobacter pylori, which adheres to gastric cells mucus, damaging the cells after colonization, and producing the rupture of the mucosal barrier; which in turn favours peptic ulcer disease. The use of non-steroidal antiinflammatory drugs (NSAID) can act at several levels; the most important one seems to be the alteration of prostaglandins synthesis and consequent decrease of mucus and bicarbonate secretion. At the same time NSAID can cause antro-pyloric motor disturbances which contributes to peptic ulcer development. The understanding of all those pathophysiological factors has promoted the designs of new pharmacological approaches to the medical treatment of peptic ulcer, so new antiulcer drugs can act at different stages of peptic-acid secretion, like H2-antagonists, proton-pump blockers, cytoprotector drugs and antimicrobial agents for Helicobacter pylori eradication.
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PMID:[Physiopathological basis for the treatment of peptic ulcer]. 215 74


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